Enhanced energy metabolism and developmental signaling in neonatal brains of female piglets parenterally-fed with 18-carbon n-3 fatty acid-based Vegaven compared with fish oil-containing lipid emulsion

Background Vegaven, an intravenous lipid emulsion based on 18-carbon n-3 fatty acids, reduces the accumulation of lipopolysaccharide (LPS) in brains of parenterally-fed piglets compared with fish oil-containing SMOFlipid. Since inflammation impairs brain energy metabolism and growth signaling, this study compared key metabolic and developmental signaling pathways with the use of different lipid emulsions for parenteral nutrition (PN). Methods 3-4-day-old female piglets were randomized to isocaloric isonitrogenous PN with Vegaven (VEGA, N=10) or SMOFlipid (SMOF, N=9). After 14 days of PN, plasma and tissue samples were collected. Results LPS and TNF-α were lower in brain tissue samples (prefrontal cortex) of VEGA versus SMOF. Brain pyruvate dehydrogenase activity, and the ketone body β-hydroxybutyrate in both liver and brain were higher in VEGA. In contrast, there was higher phosphorylation and activation of AMP-activated protein kinase (p Thr172 AMPK), a sensor of energy stress and master regulator of catabolic metabolic pathways, in brain samples of SMOF without compensatory increase in fatty acid oxidation. Anabolic signaling in the brain was higher in VEGA versus SMOF, as indicated by higher insulin receptor substrate-1 (IRS1) and Akt substrate of 160 kDa (AS160) abundance, and higher phosphorylation of mammalian target of rapamycin (p Ser2448 mTOR), essential for axon growth, dendrite arborization, and memory function. The transcription factors cAMP-response-element-binding-protein-1 (p Ser133 CREB1) and c-Jun, critical for brain development, showed higher nuclear abundance in brain samples of VEGA versus SMOF. Conclusions In neonatal brains of parenterally-fed female piglets, Vegaven reduced inflammation and enhanced energy metabolism and developmental signaling compared to SMOFlipid.